title: Involvement of P2Y6 receptor in p38 MAPK-mediated COX-2 expression in response to UVB irradiation of human keratinocytes.
abstract: Ultraviolet B (UVB) radiation induces inflammation in human skin. Extracellular nucleotides are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. In this study, we investigated the involvement of extracellular nucleotides and P2 receptors in UVB-radiation-induced inflammation using human keratinocyte-derived HaCaT cells. UVB radiation induced rapid ATP release from HaCaT cells; this was inhibited by pretreatment with anion transporter blockers or maxi-anion channel blockers. In addition, the radiation-induced activation of p38 MAPK was significantly blocked by pretreatment with ecto-nucleotidase (apyrase) or P2Y6 receptor antagonist (MRS2578). Expression of COX-2, mediated by activation of p38 MAPK, was also induced by UVB radiation. Both pretreatment with MRS2578 and knockdown of the P2Y6 receptor by siRNA transfection attenuated the induction of COX-2 in HaCaT cells exposed to UVB radiation. Our results indicate that UVB radiation evokes ATP release from human keratinocytes and also that activation of P2Y6 receptor mediates the UVB-radiation-induced activation of p38 MAPK and expression of COX-2. Thus P2Y6 receptor is a mediator of UVB-radiation-induced inflammatory responses in keratinocytes.
authors.affiliation: Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi Chiba, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Takai
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tsukimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Harada
authors.forename: Shuji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D058914:Purinergic Antagonists / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D058914:Purinergic Antagonists; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D000255:Adenosine Triphosphate; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases